Effects of 1 a(OH)-vitamin D₃ and 24,25(OH)₂-vitamin D₃ on long bones of glucocorticoid-treated rats

Glucocorticoids may induce osteopenia in experimental animals and in man. In order to study the possible effects of vitamin D metabolites in the prevention of glucocorticoid-induced osteopenia in rats, we administered lα(OH)-vitamin D₃ 24,25(OH)₂-vitamin D₃ or a combination of both metabolites, by intragastric intubation, to rats treated daily by intramuscular injections of 10 mg/kg cortisone acetate. Treatment with the vitamin D metabolites started after 1 month of glucocorticoid therapy, at the time osteopenia was already present. Cortisone acetate decreased the gain weight, increased alkaline phosphatase (AP) and decreased Ca serum levels. It also decreased tibial wet and ash weight and tibial Ca content. Computerized histomorphometry of sections from the upper tibia showed decreased epiphyseal bone volume and increased bone marrow volume; decreased height of hypertrophic cartilage in the growth plate and decreased amount of persisting cartilage in the metaphyseal bone trabeculae were also observed. Administration of 24,25(OH)₂D₃ alone did not reduce these glucocorticoid-induced bone changes and sometimes even worsened them. lα(OH)D₃ reversed many of the deleterious effects of cortisone acetate. It reduccd serum AP levels, increased serum Ca levels, increased bone ash weight, epiphyseal and metaphyseal bone volume, with a concomitant reduction in epiphyseal and metaphyseal bone marrow volume. The best results were obtained by a combi-nation of lα(OH)D₃ and 24,25(OH)₂D₃. It is presumed that both metabolites are needed to reduce the impact of glucocorticoids on bone. 1α(OH)₂D₃ acts on the gut. increasing Ca absorption (which was decreased by glucocorticoids), and 24,25(OH)₂D₃, directly acts on bone to enhance bone formation and mineralization.